The Virology Program Project at the Cancer Research Center of the Univ. of North Carolina is an interdisciplinary program involving the Departments of Medicine, Bacteriology and Immunology, Pediatrics, Pathology, Genetics and Biochemistry. Epstein-Barr Virus. DNA Studies: We have continued characterization of the viral DNA obtained from superinfected Raji cells. A new project involves determination of the nucleosomal structure of Epstein-Barr virus DNA in lymphocyte lines. During the past year we have begun studies with the new antiviral drug, acycloguanosine. With this drug, we have recovered for the first time supercoiled EBV genomes from the HR1 virus-producing cell line and obtained restriction endonuclease patterns of the supercoiled DNA recovered from these cells. The drug has no effect on the maintenance of the episomal form of the EBV genome. Protein Studies: We have begun isolation and functional characterization of the EBV nuclear antigen (EBNA) and identification of the non-histone proteins whose synthesis appears to be stimulated in Raji cells superinfected with EBV. Pathobiologic and Immunologic Studies: We have concentrated on study of EBV-induced alterations of the lymphocyte membrane and generation of cytotoxic lymphocytes by three viral antigens in vitro. In addition, we have studied the effect of phosphonoacetic acid on the transformation of cord-blood lymphocytes by EBV with a view toward understanding whether a round of viral DNA replication is required for transformation. Our studies of the epithelial target cells of EBV replication in man continue. We are studying the replication of mouse CMV in tracheal organ cultures, and have discovered that mice which are resistant to murine CMV in tracheal organ cultures, and have discovered that mice which are resistant to murine CMV are apparently resistant to infection on the cellular level. Cytomegalovirus and Other Herpes-Group Viruses: Dr Huang's laboratory has continued work with purification and characterization of herpes simplex virus-induced DNA polyymerase, varicella-zoster virus-induced DNA polymerase and with several cytomegaloviruses from other animal species. The objective of this work continues to be a study of the relatedness of the various virus-induced polymerases in the herpes-group viruses.